AVS 68 Session CA+AS+SE+SS-TuM: Progress and Challenges in Industrial Applications

XPS is a well-established technique used for non-destructive analysis of the chemical composition of thin layers and interfaces and is most commonly performed using Al Kα radiation (1486.6 eV), which limits the analysis to the top 5-10nm. The recently developed laboratory-based hard X-ray photoelectron spectroscopes (HAXPES) provide new analysis options. They enable the analysis of thicker film structures and interfaces buried down to 20-50 nm depending on the photon energy and facilitate the analysis of fragile buried layers without ion-induced chemical damage.

This new in-lab technology however comes with new challenges. By the increase of effects which were less pronounced or did not play a role in the analysis with soft X-ray photoelectron spectroscopy the exact binding energy determination and hence analysis of chemical bonding inside layers and at interfaces is more challenging. The recoil effect for instance, which is related to preservation of momentum, resulted in electron energy shifts well within the error bar of peak position determination for XPS spectra. For HAXPES, the recoil effect has to be taken into account, especially when examining low Z materials. Charging effects play a bigger role as well. While charging has to be taken into account for XPS, the analysis of most XPS spectra is quite straightforward as long as the surface charge is stable and the lateral distribution of surface charge is uniform within the area of analysis. For HAXPES however vertical charge distribution comes into the game for a large group of structures whose development can benefit from HAXPES analysis. Vertical charge build up can be complex, especially if examined structures exist of multiple layers and hence multiple interfaces, containing a large variety of materials. But even in ‘simple’ non-conducting one-layer structures a vertical charge gradient builds up when exposed to X-rays and small changes in the parameters of standard surface charge neutralization techniques - as the use of e-beam flood guns - can influence the nature of the charge gradient.

HAXPES spectra of technologically relevant samples will be discussed to demonstrate the challenge of determining exact binding energy values. The set of examined samples comprises complex oxide layers with varying thickness on Si samples and metal/high-k/Si stacks including high-k materials as HfO₂. All experiments are performed in a PHI Quantes system and/or a Scienta Omicron HAXPES Lab, both equipped with two monochromatic X-ray sources: an Al Kα (1486.6 eV) and a Cr Kα (5414.8 eV - Quantes) or Ga Kα (9252.1 eV – HAXPES lab) X-ray source.

Acknowledgement

We are grateful to the Research Foundation Flanders (FWO) for funding the HAXPES Lab instrument within the HERCULES program for Large Research Infrastructure of the Flemish government. Project I014018N.

Tissue is highly organized with diverse cells that interact and communicate. Together with numerous biomolecules (e.g. metabolites and lipids) of cellular processes‚ the multilevel heterogeneities drive the biological function and disease-associated discoordination^1-2. This spatial complexity is often ignored by traditional tissue assay. Mass spectrometry imaging holds the potential to visualize the heterogeneous cell organization and biomolecules in their context. However‚ it is challenging to achieve high spatial resolution and high chemical sensitivity toward different biomolecules. Moreover‚ the correlation of spatial omics in a single sample is impossible due to the difficulty of preserving the fast-changing metabolites.

To overcome these analytical hurdles‚ innovative technology and methodology are developed for omics imaging in single cells. On the same frozen-hydrated tissue‚ successive (H₂O)_{n (n>28k)}-GCIB-SIMS and C₆₀-SIMS imaging are employed to profile untargeted metabolites/lipids and targeted proteins by lanthanides antibodies (~ 40 in one acquisition) at 1 µm resolution. The novel ion source‚ (H₂O)_n(n>28k)-GCIB enhances chemical sensitivity‚ improves beam focus‚ reduces matrix effect‚ and extends detection ranges up to m/z 6000 ^3-12. Coupled with cryogenic analysis‚ the tissue is analyzed at near nature state‚ retaining the spatiotemporal distribution of metabolites and lipids. The AI-aided computational processing is used to register the omics in different cell types for further discriminant analysis.

With the new development‚ a number of tissues are imaged. On breast cancer tissue‚ the high population of macrophages (CD68) and less infiltration of immune cells (CD45‚ CD4) are observed‚ as well as the variation of the metabolic state in different cells. Several phosphatidylinositol species are concentrated in the epithelial tumor cells (pan-cytokeratin)‚ along with desaturated lipids and GSH‚ indicating the mechanism of immune resistance and antioxidation for tumor survival ²⁷. Eight ganglioside GM3s correlate with the Ki-67 expressing cells‚ likely the markers of neoplastic transformation of breast tissue³⁷. On liver tissue‚ distinct lipid clusters colocalize with periportal and pericentral proteins‚ and metabolic and lipidomic signature varies in distinct liver cells (e.g.‚ sinusoidal‚ Kupffer‚ hepatocytes‚ Ito stellate‚ immune cells). Similar to protein markers‚ further clustering analysis shows that metabolites and lipids classify the cell types for the first time. The multimodal SIMS imaging opens broad applications for exploring various biological phenomena of cellular/biomolecular interactions in health/disease.

Laser-pulsed atom probe tomography (LAPT) is a powerful tool for materials characterization due to its desirable combination of high spatial resolution and analytical sensitivity. In state-of-the-art LAPT, the thermal pulse resulting from a near-ultraviolet (NUV) laser (E=3.5 eV to 3.6 eV; λ=355 nm to 343 nm) incident on the sample provides the energy to overcome the activation barrier for field ion evaporation.LAPT has been used successfully to characterize a wide range of materials including metals, semiconductors, insulators, biological materials, and even liquids. However, the thermal process is not without drawbacks. LAPT data quality can be degraded due to for example: thermal tails that limit sensitivity; the formation of cluster ions that may have isobaric overlap with elemental species; undetected neutral species which can adversely influence composition measurements; and unresolvable multiple hits which result in a loss of information. Data loss due to multiple hits and neutral species is particularly problematic for many ionic and covalent materials; it can limit the recovery of bulk stoichiometry or composition to a narrow range of experimental conditions, if at all [1,2].

Ionizing radiation in the extreme ultraviolet (EUV) region of the electromagnetic spectrum (E=10 eV to 100 eV; λ=124 nm to 12 nm) offers potential new field ionization pathways (e.g. direct photoionization and Auger decay) for atom probe tomography.Much of the EUV photon energy band is above the work function and ionization potential of any naturally occurring element, and photoionization cross-sections peak in the EUV band across the entire periodic table [3]. EUV is also highly absorbed within only the first few nm of the sample surface.

Instrument design and results from the world’s first EUV radiation-pulsed atom probe microscope are presented. This instrument uses tunable wavelength (photon energy) femtosecond-pulsed coherent EUV radiation from phase-matched high harmonic generation in a hollow waveguide. Initial experiments demonstrate successful EUV (E=41.85 eV; λ=29.6 nm) radiation-pulsed field ion emission in a variety of materials systems. Time-independent background levels, delayed evaporation tails, peak widths, charge state ratios, multiple hit counts, and the relative number of cluster ions will be compared to NUV LAPT experiments on the same samples and specimens.

[1] Mancini, L. et al. J. Phys. Chem. C118 (2014) 24136.

[2] Diercks, D.R. et al. J. Appl. Phys.114 (2013) 184903.

[3] Yeh, J.-J. and I. Landau. At. Data Nucl. Data Tables32 (1985) 1.